Oxford made it a perfect start to the season by beating Southend for the first time in their last seven attempts.
While the Shrimpers have lost their first two league games, Oxford have now knocked Bournemouth out of the Johnstone's Paint Trophy, and chalked up successive league victories.
Oxford boss Chris Wilder said following the 2-0 win: "It was another decent night's work for us, a really satisfying win.
"I thought we played really well, playing it from side to side. We know more than anyone how difficult it can be with ten men for so long because it happened to us against Swindon last season.
"It just needed us to finish off a few more opportunities. But to have a fit and free-scoring Alfie Potter and a fit and free-scoring Tom Craddock is great for us."
Southend had midfielder Michael Timlin dismissed on 27 minutes for a second yellow card, after tripping Jake Forster-Caskey - and that came just five minutes after his first booking.
Shrimpers manager Paul Sturrock said: "In the first 25 minutes we just seemed to be settling ourselves down when the red card came. I thought the second one was a soft yellow card. It changed the whole complexion of the game.
"I was proud of my players because every one of them gave a shift. But it wasn't easy with 10 players against 11 players for that long.
"At 1-0 I had to stick two forwards up to see if we could get something and we paid the price with their second goal.
"The shoe was on the other foot here in the Johnstone's Paint Trophy last season when Oxford went down to 10 men and then 9 men against us, and it is very difficult in that situation."